Journal article

The MURAL collection of prostate cancer patient-derived xenografts enables discovery through preclinical models of uro-oncology

Gail P Risbridger, Ashlee K Clark, Laura H Porter, Roxanne Toivanen, Andrew Bakshi, Natalie L Lister, David Pook, Carmel J Pezaro, Shahneen Sandhu, Shivakumar Keerthikumar, Rosalia Quezada Urban, Melissa Papargiris, Jenna Kraska, Heather B Madsen, Hong Wang, Michelle G Richards, Birunthi Niranjan, Samantha O'Dea, Linda Teng, William Wheelahan Show all

NATURE COMMUNICATIONS | NATURE PORTFOLIO | Published : 2021

Abstract

Preclinical testing is a crucial step in evaluating cancer therapeutics. We aimed to establish a significant resource of patient-derived xenografts (PDXs) of prostate cancer for rapid and systematic evaluation of candidate therapies. The PDX collection comprises 59 tumors collected from 30 patients between 2012-2020, coinciding with availability of abiraterone and enzalutamide. The PDXs represent the clinico-pathological and genomic spectrum of prostate cancer, from treatment-naïve primary tumors to castration-resistant metastases. Inter- and intra-tumor heterogeneity in adenocarcinoma and neuroendocrine phenotypes is evident from bulk and single-cell RNA sequencing data. Organoids can be cu..

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Grants

Awarded by National Health and Medical Research Council, Australia


Awarded by US Department of Defense through the Prostate Cancer Research Program


Awarded by Department of Health and Human Services through the Victorian Cancer Agency


Awarded by Prostate Cancer Foundation of Australia


Awarded by Peter MacCallum Cancer Foundation


Awarded by CASS Foundation


Awarded by Movember and National Breast Cancer Foundation Collaboration Initiative Grant


Funding Acknowledgements

We wish to acknowledge the Traditional Owners of the lands on which these studies were done. We pay our respects to their Elders, past and present. We also acknowledge the members of the Prostate Cancer Research program, the patients, families, and consumers who support our research. We acknowledge the patient representatives, clinical co-ordinators, scientists, and clinicians, who contribute to the Melbourne Urological Research Alliance (MURAL) and its collection of patient-derived models. We acknowledge kConFab including kConFab research nurses and staff, the heads and staff of the Family Cancer Clinics, and the Clinical Follow-Up Study (which has received funding from the NHMRC, the National Breast Cancer Foundation, Cancer Australia, and the National Institute of Health (USA)) for their contributions to this resource, and the many families who contribute to kConFab. We thank Mark McCabe, Chia-Ling Chan, and Alex Swarbrick for providing access to targeted DNA sequencing technology; Kathryn Alsop, Damien Bolton, Nathan Lawrentschuk, Ross Snow, and Sri Apu for provision of clinical samples; and Melissa Bullock for technical support. This work was supported by the National Health and Medical Research Council, Australia (1102752, 1090204, 1138242, 1185616, 1077799, 1156570, 1140222, 1059855, and 1121057; the US Department of Defense through the Prostate Cancer Research Program (G.P.R. W81XWH1810349; opinions, interpretations, conclusions, and recommendations are those of the authors and are not necessarily endorsed by the Department of Defense); Department of Health and Human Services acting through the Victorian Cancer Agency (MCRF15023, MCRF18017, MCRF18012, MCRF17005, L.F. MCRF16007, CAPTIV Program); Prostate Cancer Foundation of Australia (YI 0417, PIRA1519, NCG1616); Peter MacCallum Cancer Foundation (1752); Monash University (Bridging Fellowship L.P.); the CASS Foundation (7139, 8669, 8575); the EJ Whitten Foundation; Movember Foundation (Global Action Plan 1); Movember and National Breast Cancer Foundation Collaboration Initiative Grant (MNBCF-17-012); Movember and MRFF UpFront PSMA Prostate Cancer Research Alliance (PCRA); the Peter and Lyndy White Foundation; and TissuPath Pathology. This research was supported by the Monash University Histology Platform, Monash University Animal Research Laboratories, Monash Biomedicine Discovery Institute Organoid Program, and the NeCTAR Research Cloud, a collaborative Australian research platform supported by the National Collaborative Research Infrastructure Strategy.